疱疹病毒感染与免疫逃逸研究生201512ppt课件.ppt

* 疱疹病毒感染过程中所诱导产生的中和抗体不仅为某些成员如HSV-1/HSV-2型别鉴定提供了血清学依据，同时也为从免疫学角度控制疱疹病毒感染提供了技术支持。 * HSV-1侵入机体后, 宿主会迅速产生一系列反应来抵抗HSV 的感染。 * * 在病毒与机体作用的过程中， HSV-1常常能先于机体免疫系统而采取更为聪明的手段，因而机体的免疫反应常常处于下风。 HSV-1逃避免疫监控的机制。 * 人体少数组织和器官是免疫细胞不得介入的享有免疫豁免特权的部位, CNS的血- 脑脊液屏障限制了淋巴细胞进入CNS, 因而不易被T 淋巴细胞所识别， 病毒在不引起局部炎症反应的情况下在该部位可以暂时避开免疫系统的监视。 * * ICP47在病毒感染过程中产生的时间决定了其不可能作用于HSV感染时免疫反应的全过程 VHS蛋白也能与ICP47一起干扰MHC I 类分子的抗原递呈 ICP47虽然不能辅助于HSV感染的全过程，但至少可以为感染赢得一定的时间和空间，免受免疫系统的攻击。 TAP（transporter associated with antigen processing ） * T细胞之间存在着通过细胞---细胞之间的分子接触而发挥免疫调控作用的途径，也是HSV免疫干扰的靶点。 具体机理还不清楚 * * * SeV infection activates IRF3 and it translocates from the cytoplasm to the nucleus However, Co-transfection of US11 block the nuclear translocation of IRF3, but does not affect the resting IRF3. As we know that phosphorylation and dimerization of IRF3 is critical for IFN-beta production, US11 inhibits both the phosphorylation and dimerization of IRF3. So US11 could impede IRF-3 activation * In the RLR mediated signaling pathway, TRAF3 links upstream IFN signaling responses of MAVS to TBK1. The K63-linked polyubiquitination of TRAF3 is crucial for signaling by MAVS and recruitment of TBK1. The presence of UL36USP reduced the SeV induced ubquitination of TRAF3, whereas the C40A mutant did no affect the ubiquitination level of TRAF3. UL36USP could inhibit both K48- and K63-linked ubiquitination of TRAF3 Co-transfection UL36USP, but not the C40A mutant, inhibited the SeV induced recruitment of TBK1 by TRAF3 * DLR and semi-quantitative PCR showed US3 inhibited SeV-mediated activation of the IFN-β promoter activity US3 inhibited the SeV mediated dimerization of IRF3 US3 also inhibited IRF3 and IFN stimulated response element (ISRE) promoter activity induced by SeV infection The K220 of HSV-1 US3 is critical for its ATP binding and the D305 is critical for its catalytic activity K220M or D305A mutation failed to inhibit SeV mediated activation of IFN-β, PRD(III-I) and ISRE promoter activity By semi-quantitati